Gene expression and autoradiographic localization of endothelin-1 and its receptors A and B in the different zones of the normal human prostate.

PURPOSE: To investigate the gene expression and tissue distribution of prepro Endothelin-1 (ET-1), Endothelin Converting Enzyme (hECE-1), and ETA and ETB receptors in the central (CZ), transition (TZ) and peripheral (PZ) zones of normal human prostates. MATERIALS AND METHODS: Sections of the different zones of histologically normal prostates from 35 year-old men were obtained and autoradiographically studied with 125I ET-1 with and without the ETA antagonist BQ-123, the ETB agonists sarafotoxin 6C, and excess cold ET-1. Specimens from PZ and CZ and DU145 and PC3 human prostate cancer cell lines were also investigated by reverse transcription (RT)-PCR. RESULTS: The mRNAs of all genes were detected in all specimens examined. No ETB expression was found in either cell lines. Specific intense 125I ET-1 binding with clear-cut differences among zones was found. In the CZ the main subtype in the glandular stroma and epithelium was the ETA and ETB, respectively, in the PZ the opposite was true. In PZ, the ETA receptors were detected on the glandular epithelium; in the TZ both receptor subtypes were only in the stroma. CONCLUSIONS: These receptors' zonal distribution differences may be relevant for the pathogenesis of BPH and prostatic cancer.